Heart valve prostheses are well-known in the art as replacement mechanical valve devices for damaged or diseased natural heart valves. Bileaflet valves are a familiar example of an artificial heart valve to those skilled in the art. Among bileaflet valves, the St. Jude Medical Valve ("SJMV") or Prosthesis is well-known, having served as a replacement for hundreds of thousands of aortic and mitral heart valves since its introduction in 1977.
The SJMV is a popular choice for cardiac valve replacement because of its low-profile design and good hemodynamics. Statistically, the St. Jude valve has shown excellent performance in recipients of the valve. However, implantation of the SJMV may yield more sub-clinical hemolysis (disruption of red blood cells) in valve recipients than other comparable prostheses. Moreover, in a number of unexplained cases, SJMV recipients have developed serious hemolysis requiring reoperation, explantation, and replacement of the valve.
Sub-clinical hemolysis is common following the implantation of most types of artificial heart valves. The hemolysis has usually been attributed to mechanical shearing forces on erythrocytes (red blood cells) in the turbulent flow which may develop within the artificial heart valve prosthesis. The turbulence arises as blood moves through the zone of pressure gradient across the valve prosthesis. Leakage alongside the valve (paravalvular leakage) due to imperfect sutures or dehiscence (becoming loose) is also known to cause undesirable turbulence and hemolysis owing to the "jet effect." The shear forces act mechanically to damage the red blood cells, causing breakage which releases free hemoglobin and the enzyme lactic dehydrogenase (LDH) into the blood. This loss of red blood cells makes the marrow "push" immature erythrocytes ("reticulocytes") into the circulation.
Subclinical hemolysis is usually compensated for by increased bone marrow red blood cell production. Drug treatment such as iron therapy can also help. On the other hand, hemolysis may become life-threatening when severe anemia develops. Anemia, in turn, may both worsen the hemolysis and create iron-deficient red blood cells which are more vulnerable to damage. If not treated, significant hemolysis may lead to heart and renal (kidney) failure and eventually death. The treatment for severe hemolysis in SJMV recipients usually includes the hazardous reoperation and replacement of the hemolytic SJM valve.
Therefore, the cases of severe hemolysis accompanying SJMV replacement, while few in number, are a serious concern. Various studies have attempted to find the cause of this inexplicable severe hemolysis. While the studies have proffered a variety of explanations for some of the instances of hemolysis, other instances have gone unexplained. For instance, Kingsley et al. in "St. Jude Medical Valve Replacement" J. Thorac. Cardiovasc. Surg. 1986; 92:349-360, reports one SJMV recipient developing acute anemia necessitating blood transfusions. The patient had marked hemoglobinuria and renal failure. All other causes of hemolysis were excluded before re-operation and replacement of the SJMV with a xenograft (animal tissue) ten days after the first operation. No further hemolysis occurred. The explanted SJMV was analyzed at St. Jude Medical Laboratories and found to be structurally normal.
Five more cases of unexplained severe hemolysis in recipients of the SJMV are revealed by Taggart et al., in "Severe Haemolysis with the St. Jude Medical Prosthesis," Eur. J. Cardio-thorac. Surg. 1988; 2:137-142. No paravalvular leakage was found by echocardiography, or seen at re-operation, or at autopsy examination in those who died before reoperation could be effected. The explanted valves functioned satisfactorily in laboratory hemodynamic testing. Hemolytic anemia without paravalvular leakage was also reported in three SJMV recipients by Burckhardt et al., in "Heart Valve Replacement with St. Jude Medical Valve Prosthesis," Valvular Heart Disease Sept. 1988; 78:118-124.
The hemolysis accompanying the St. Jude valve has also been attributed to asynchronous closure of the valve leaflets causing excessive turbulence (Ferriere, "Hemolysis in Patients with Valve Prostheses, Comparison Between Bjork-Shiley and St. Jude Medical Prostheses," Arch. Mal. Coeur 1985; 78:1243.
Furthermore, scanning electron microscopy (SEM) has been utilized to study the flat surfaces of two St. Jude valves explanted from recipients who developed severe hemolysis. Both patients died (Morishita et al., "Fatal Hemolysis Due to Unidentified Causes Following Mitral Valve Replacement with Bi-Leaflet Tilting Disk Valve Prosthesis," Heart Vessels 1987; 3:100-103). The SEM identified a smooth elevated irregularity on the flat valve leaflet surface suspected of causing the severe hemolysis.
While SEM is desirable for studying aspects of heart valve prosthesis leaflets, its usefulness is circumscribed. For instance, SEM normally requires an irreversible deposition of gold or osmium upon an object to be studied. Thus, the use of SEM to screen SJMVs before implantation is impractical. Moreover, SEM analysis, even with the deposition of gold, may not provide information on some potentially important features of SJMVs, such as surface profile characteristics.
Despite various attempts to discover the causes of hemolysis in recipients of bileaflet heart valves, instances of serious hemolysis have gone unexplained in spite of rigorous study.
It is an object of this invention to provide an improved method of making heart valve prostheses to ensure uniform quality control of heart valve components.
It is a further object of this invention to provide for an improved method of making heart valve prostheses to identify heart valve prostheses that may cause hemolysis and to exclude or modify them to conform to a predetermined standard.
A final object of this invention is to understand the source of hemolysis in bileaflet tilting heart valve prostheses, and use that understanding in future valve design to reduce hemolysis in patients in whom those valves may be implanted.
These and other objects of the invention will be understood more clearly by reference to the following detailed description and drawings.